Risk of relapse after antidepressant discontinuation in anxiety disorders, obsessive-compulsive disorder, and post-traumatic stress disorder: systematic review and meta-analysis of relapse prevention trials

Abstract

Objectives To examine the risk of relapse and time to relapse after discontinuation of antidepressants in patients with anxiety disorder who responded to antidepressants, and to explore whether relapse risk is related to type of anxiety disorder, type of antidepressant, mode of discontinuation, duration of treatment and follow-up, comorbidity, and allowance of psychotherapy. Design Systematic review and meta-analyses of relapse prevention trials. Data sources PubMed, Cochrane, Embase, and clinical trial registers (from inception to July 2016). Study selection Eligible studies included patients with anxiety disorder who responded to antidepressants, randomised patients double blind to either continuing antidepressants or switching to placebo, and compared relapse rates or time to relapse. Data extraction Two independent raters selected studies and extracted data. Random effect models were used to estimate odds ratios for relapse, hazard ratios for time to relapse, and relapse prevalence per group. The effect of various categorical and continuous variables was explored with subgroup analyses and meta-regression analyses respectively. Bias was assessed using the Cochrane tool. Results The meta-analysis included 28 studies (n=5233) examining relapse with a maximum follow-up of one year. Across studies, risk of bias was considered low. Discontinuation increased the odds of relapse compared with continuing antidepressants (summary odds ratio 3.11, 95% confidence interval 2.48 to 3.89). Subgroup analyses and meta-regression analyses showed no statistical significance. Time to relapse (n=3002) was shorter when antidepressants were discontinued (summary hazard ratio 3.63, 2.58 to 5.10; n=11 studies). Summary relapse prevalences were 36.4% (30.8% to 42.1%; n=28 studies) for the placebo group and 16.4% (12.6% to 20.1%; n=28 studies) for the antidepressant group, but prevalence varied considerably across studies, most likely owing to differences in the length of follow-up. Dropout was higher in the placebo group (summary odds ratio 1.31, 1.06 to 1.63; n=27 studies). Conclusions Up to one year of follow-up, discontinuation of antidepressant treatment results in higher relapse rates among responders compared with treatment continuation. The lack of evidence after a one year period should not be interpreted as explicit advice to discontinue antidepressants after one year. Given the chronicity of anxiety disorders, treatment should be directed by long term considerations, including relapse prevalence, side effects, and patients’ preferences.

The Efficacy of a Group CBT Relapse Prevention Program for Remitted Anxiety Disorder Patients Who Discontinue Antidepressant Medication: A Randomized Controlled Trial

“…However, recurrence rates following discontinuation are high. A recent meta-analysis showed that, in the medium term, continuing AD results in lower recurrence rates (16%) than discontinuing AD (36%) [3]. Strategies to prevent recurrence are needed, but lacking.…”

Failure to Respond after Reinstatement of Antidepressant Medication: A Systematic Review

“…The proportion of response failure across these studies were 9.1 [37], 42.9 [42], 10 [41], and 18.9% [43], respectively. An argument in favor of this disease progression hypothesis is that the proportion of response failure seems to be comparable to occurrence rates during maintenance treatment [24,25]. However, since there is no direct comparison with maintenance therapy, the studies included in this review cannot substantiate this hypothesis.…”

“…Although a failure to respond only seems to occur in a minority of patients restarting antidepressants (16.5%, range 3.8-42.9%), it is of clinical relevance given the high number of patients taking antidepressants [1], the occurrence of the phenomenon in all common classes of antidepressants, the high prevalence of anxiety disorders, depressive disorders, OCD, and PTSD [11], and the tendency of these disorders to run a chronic course in which the occurrence of symptoms is common [24,25,54,[59][60][61][62][63][64][65][66][67][68][69][70].…”

“…This situation frequently occurs in daily clinical practice because: (1) anxiety and depressive disorders are highly prevalent [11], (2) up to two thirds of patients receive antidepressants [1], (3) many patients achieve remission while on antidepressant medication [12][13][14][15][16][17][18][19][20][21][22], (4) treatment guidelines advise discontinuation after a period of sustained remission [12,[14][15][16][17][18][19][20][21][22][23], (5) and 36 or 41% of patients with, respectively, anxiety disorders or depressive disorders experience symptoms following antidepressant discontinuation [24,25]. These are often labelled as relapse, but according to Chouinard and Chouinard [26] these symptoms can also be explained as newly occurring symptoms caused by the withdrawal of antidepressants.…”

Posttraumatic stress disorder among patients with oral and maxillofacial trauma in a South Indian population

“…15 Sometimes, patients who have discontinued therapy for depression also exhibit PTSD. 16 Patients with PTSD run a risk of developing respiratory, cardiovascular, gastrointestinal, and autoimmune complications. 17 PTSD can have wide ranging repercussions not only on the victim's family but also on the society in general.…”